Deficient phospholipase C activity in blood polimorphonuclear neutrophils from patients with liver cirrhosis

Background/Aims Circulating neutrophils from cirrhotic patients have a reduced capacity to generate superoxide anion (O2−), which might contribute to frequent bacterial infections in these patients. We studied the signal transduction pathways involved in the generation of O2− in neutrophils from 98 cirrhotic patients and 46 healthy controls. Methods We measured O2− production in neutrophils induced by fMLP, opsonized zymosan, TNFα, NaF, AlF4−, A23187 and phorbol myristate acetate. Furthermore, we measured phospholipase C activity in neutrophils from healthy controls and end-stage cirrhotic patients. Results O2− production was decreased in neutrophils from patients in response to fMLP, opsonized zymosan and TNFα. Likewise, response of these cells to G-protein stimulation by fluorides was also decreased. These reduced responses correlated significantly with the degree of liver dysfunction. On the contrary, neutrophils from patients responded normally to A23187 and phorbol esters stimulation indicating that Ca2+- and PKC-dependent pathways are intact in these cells. Finally, phospholipase C activity was markedly reduced in neutrophils from end-stage liver cirrhosis. Conclusions These data confirm that O2− generation by neutrophils is decreased in patients with cirrhosis, particularly in those with more severe liver dysfunction, and suggest that this defect involves phosphatidylinositol specific phospholipase C activity.